10.4 THE HUMAN GENOME PROJECT AND THE ULTIMATE MAP

The goal of determining the complete DNA sequence of the human genome has captured the imagination of many
geneticists as well as other biomedical scientists
(Kevles and Hood, 1992;
Wills, 1992). It was this goal that originally catapulted the
"Human Genome Project" into the headlines of newspapers and the talk of politicians in the US and elsewhere
during the latter part of the 1980s. In 1990, the National Institutes of Health and the Department of Energy
began a coordinated effort to reach this goal within a period of 15 years by stepping through a series of
intermediate goals. In 1993, Francis Collins, the new director of the National Center for Human Genome Research
at NIH, outlined the newest version of a 5 year plan for this project
(Collins and Galas, 1993). The 5-year goals incorporated into this plan
include: (1) a high resolution linkage map at a resolution of 2-5 cM with an established set of easy to use DNA
markers; (2) a high resolution physical map with Sequence Tagged Site (STS) markers located every 100 kb; (3)
improvements in DNA sequencing technology to allow the annual accumulation of 50 megabases of sequence; (4) the
development of efficient methods for gene identification within cloned sequences, and for the mapping of genes
identified by other means; and (5) further development of technology for increased automation, increased use of
robotics, and more sophisticated computer-based tools for information management and analysis.

Although the Human Genome Project is focused, of course, on the human, there is a uniform consensus among
researchers that it is only in comparison with the genomes of model organisms such as the mouse that the human
genome will reveal all of it secrets. Thus, another primary goal of the human genome project is to sequence
selected segments of the mouse genome side by side with homologous regions of the human genome. By evaluating
the relative level of conservation across a genomic region and combining this information with other computational
assessments of sequence content, it will become possible to uncover essentially all genes, promoters, enhancers,
and other regulatory elements. Unknown, and unexpected, non-coding, sequences that show conservation indicative
of biological function are sure to be identified as well, and further studies will be required to understand the
functions of these new elements.

Even if the Human Genome Project meets its target of a complete human sequence by the year 2005, in the minds of
geneticists, the ultimate map of the genome will extend far beyond the sequence alone and will require many
more years to attain. This ultimate map will show all genomic regions that are subject to parental imprinting, all
regions that show methylation, and the locations of all DNase I hypersensitivity sites that appear in the context
of the chromatin structure which forms around the DNA molecule. Finally, the complete sequence will be used as a
jumping board to map the entire network of genetic and gene product interactions that occur during the development
of a human being, with a determination of the complete pattern of expression of every single gene through both time and space.

Will such an ultimate map ever be attained? It is impossible to predict in 1994 as these words are being written.
However even if it is attained, will it really tell us something deeply profound about the state of being human? This
will only happen if it becomes possible to visualize the manner in which the whole functional network becomes more
than the sum of the parts. Will any human mind have the capacity for such a visualization? Is it our destiny to
understand the molecular biology of the human soul or, rather, to search forever in vain? These are questions that
may be answered in the 21st century, even later, or perhaps never.